Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells

Heng Yuan Tang, Ai Shih, H. James Cao, Faith B. Davis, Paul J. Davis, Hung Yun Lin

研究成果: 雜誌貢獻文章

96 引文 斯高帕斯(Scopus)

摘要

Cyclooxygenase-2 (COX-2) is antiapoptotic and is implicated in tumorigenesis. Recent reports, however, have also ascribed a proapoptotic action to inducible COX-2. We show here for the first time that a stilbene, resveratrol, induces nuclear accumulation of COX-2 protein in human breast cancer MCF-7 and MDA-MB-231 cell cultures. The induction of COX-2 accumulation by resveratrol is mitogen-activated protein kinase (MAPK; extracellular signal -regulated kinase 1/2)- and activator protein 1-dependent. Nuclear COX-2 in resveratrol-treated cells colocalizes with Ser 15-phosphorylated p53 and with p300, a coactivator for p53-dependent gene expression. The interaction of COX-2, p53, and p300, as well as resveratrol-induced apoptosis, was inhibited by a MAPK activation inhibitor, PD98059. A specific inhibitor of COX-2, NS398, and small interfering RNA knockdown of COX-2 were associated with reduced p53 phosphorylation and consequent decrease in p53-dependent apoptosis in resveratrol-treated cells. We conclude that nuclear accumulation of COX-2 can be induced by resveratrol and that the COX has a novel intranuclear colocalization with Ser 15-phosphorylated p53 and p300, which facilitates apoptosis in resveratrol-treated breast cancer cell.
原文英語
頁(從 - 到)2034-2042
頁數9
期刊Molecular Cancer Therapeutics
5
發行號8
DOIs
出版狀態已發佈 - 八月 2006
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

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